1-241500602-TGAGAGAGAGAGAGAGAGA-TGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA

Variant names:

• chr1-241500602-T-TGAGAGAGAGAGAGAGAGAGAGA
• rs144131869
• NM_000143.4:c.1237-34_1237-13dupTCTCTCTCTCTCTCTCTCTCTC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000143.4(FH):​c.1237-34_1237-13dupTCTCTCTCTCTCTCTCTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00045 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000071 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FH NM_000143.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.993

Genes affected

FH (HGNC:3700): (fumarate hydratase) The protein encoded by this gene is an enzymatic component of the tricarboxylic acid (TCA) cycle, or Krebs cycle, and catalyzes the formation of L-malate from fumarate. It exists in both a cytosolic form and an N-terminal extended form, differing only in the translation start site used. The N-terminal extended form is targeted to the mitochondrion, where the removal of the extension generates the same form as in the cytoplasm. It is similar to some thermostable class II fumarases and functions as a homotetramer. Mutations in this gene can cause fumarase deficiency and lead to progressive encephalopathy. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000448 (60/133878) while in subpopulation AFR AF= 0.00114 (40/34954). AF 95% confidence interval is 0.000863. There are 0 homozygotes in gnomad4. There are 29 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 60 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FH	NM_000143.4	c.1237-34_1237-13dupTCTCTCTCTCTCTCTCTCTCTC		intron_variant	Intron 8 of 9	ENST00000366560.4	NP_000134.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FH	ENST00000366560.4	c.1237-34_1237-13dupTCTCTCTCTCTCTCTCTCTCTC		intron_variant	Intron 8 of 9	1	NM_000143.4	ENSP00000355518.4

Frequencies

GnomAD3 genomes AF: 0.000448 AC: 60 AN: 133788 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00115

Gnomad AMI AF: 0.00115

Gnomad AMR AF: 0.0000760

Gnomad ASJ AF: 0.000611

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000492

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000219

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000708 AC: 96 AN: 1356750 Hom.: 0 Cov.: 48 AF XY: 0.0000740 AC XY: 50 AN XY: 675428

Gnomad4 AFR exome AF: 0.000383

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000123

Gnomad4 EAS exome AF: 0.0000265

Gnomad4 SAS exome AF: 0.0000743

Gnomad4 FIN exome AF: 0.000101

Gnomad4 NFE exome AF: 0.0000653

Gnomad4 OTH exome AF: 0.0000355

GnomAD4 genome AF: 0.000448 AC: 60 AN: 133878 Hom.: 0 Cov.: 0 AF XY: 0.000454 AC XY: 29 AN XY: 63862

Gnomad4 AFR AF: 0.00114

Gnomad4 AMR AF: 0.0000759

Gnomad4 ASJ AF: 0.000611

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000493

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000219

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs144131869; hg19: chr1-241663902;